An Inhaler For Electronically Supervised Parenteral Administration of a Pharmaceutical Composition

Abstract

An inhaler (400) for electronically supervised parenteral administration of a dry powder pharmaceutical composition comprising: storage means (410) for the pharmaceutical composition in a form of a dry powder; administration means (411) for ad- ministration of the pharmaceutical composition; memory (404) and processing means (402); communication means (401); controlled blocking means (403) for blocking administration of the pharmaceutical composition, wherein the inhaler (400) is adapted to receive data corresponding to an administration scheme (11), to determine whether a mobile device (300) with an authorisation token assigned thereto is present, and to control the controlled blocking means (403) so as to allow administration of the pharmaceutical composition only with compliance with the administration scheme (11) in the presence of the mobile device (300) with the authorisation token (12) assigned thereto.

1 . An inhaler for electronically supervised parenteral administration of a dry powder pharmaceutical composition comprising:
 storage means for the pharmaceutical composition in a form of a dry powder, administration means for administration of the pharmaceutical composition; memory and processing means   communication means;   controlled blocking means for blocking administration of the pharmaceutical composition, wherein   the inhaler is adapted to receive data corresponding to an administration scheme, to determine whether a mobile device with an authorisation token assigned thereto is present, and to control the controlled blocking means so as to allow administration of the pharmaceutical composition only with compliance with the administration scheme in the presence of the mobile device with the authorisation token reassigned thereto.   
     
     
         2 . The inhaler according to  claim 1  wherein the inhaler is further adapted to
 measure via sensor unit at least one physical property of the dry powder pharmaceutical composition administration process within the inhaler during an administration process and 
 communicate the measured physical property to the mobile device. 
 
     
     
         3 . The inhaler according to  claim 2  wherein the physical property of the pharmaceutical composition administration process measured within the inhaler during an administration process is an air pressure, sound intensity, vibration magnitude or any combination of such physical properties. 
     
     
         4 . The inhaler according to  claim 2  wherein the sensor unit comprises a microphone, and the measured physical property is an amplitude of a sound wave. 
     
     
         5 . The inhaler of  claim 2  wherein the sensor is pllaced inside the mixing chamber where a dry powder pharmaceutical composition is mixed with air during the inhalation. 
     
     
         6 . The inhaler according to  claim 1  wherein the uncontrolled blocking means comprises a drive unit and active actuating clement that blocks the transfer of a dose of the dry powder pharmaceutical composition from the storage to the administration unit. 
     
     
         7 . The inhaler according of  claim 1  wherein actuating element in a blocking state blocks the transferor a dose of the pharmaceutical composition from the storage to the administration unit, and in an open position allows administration of the pharmaceutical composition in response to a control signal from the control unit. 
     
     
         8 . The inhaler of  claim 1  wherein, and upon receiving a control signal from the processing unit actuating element moves into an open state and allows administration of the pharmaceutical composition. 
     
     
         9 .The inhaler according of  claim 1  wherein the blocking means comprises an element selected from a group comprising: a valve, pin. bolt, relay, key. normally closed switch. 
     
     
         10 . The inhaler according to  claim 1  wherein a dry powder pharmaceutical composition comprising ketamine or its pharmaceutically acceptable salt for use in a method of treatment of depression, by direct administration to the lungs via pulmonary route. 
     
     
         11 . The inhaler according to  claims 1  comprising ketamine or its pharmaceutically acceptable salt for use in a method of treatment of depression, wherein ketamine or its pharmaceutically acceptable salt is administered by pulmonary route as a dry powder pharmaceutical composition. 
     
     
         12 . The inhaler of  claim 10  wherein pharmaceutically acceptable salt is hydrochloride. 
     
     
         13 . The inhaler of  claim 10  wherein ketamine is esketamine hydrochloride. 
     
     
         14 . The inhaler of  claim 10  wherein the composition comprises from 2 mg to 100 mg of micronized ketamine calculated as a free base per nominal unit dose. 
     
     
         15 . The inhaler according to  claim 14  wherein composition comprises from 2 mg to 40 mg of micronized ketamine calculated as a free base per nominal unit dose. 
     
     
         16 . The inhaler according to  claim 15  wherein the composition comprises 4 mg of micronized esketamine calculated as a free base per nominal unit dose. 
     
     
         17 . The inhaler of  claim 10  wherein composition comprises one or more additives selected from the group consisting of a carbohydrate bulking agent in the amount of 30 to  95 % by weight and a stabilizing agent in the amount of 0.2 - 3% by weight, with respect to the total weight of the composition. 
     
     
         18 . The inhaler of  claim 10  wherein composition comprises ketamine having median particle diameter d50 of 1 - 10μm. d10 of 0.2 - 5μm and d90 of 3 - 35μm. as measured by laser diffraction technique. 
     
     
         19 . The inhaler according of  claim 14  adapted to provide emitted dose of at least 1.0 mg of ketamine calculated as a free base, corresponding to 1.2 mg of ketamine hydrochloride. 
     
     
         20 . The inhaler according to  claim 19  wherein the fraction 5 of the emitted dose delivered to the lungs is at least 40%. 
     
     
         21 . The inhaler of claim lO wherein the composition for administration via pulmonary route is comprised in a blister with plurality of individual nominal unit doses premetered and individually sealed. 
     
     
         22 . The inhaler of  claim 10  wherein the composition for administration via pulmonary route is comprised in a capsule with a single nominal unit dose. 
     
     
         23 . The inhaler of  claim 10  wherein the composition for administration via pulmonary route is comprised in a multi-dose powder reservoir. 
     
     
         24 . The inhaler of  claim 10  wherein the administration scheme provides a self-administration by a patient by inhalation of a dry powder ketamine composition or formulation in a sequence of administrations consisting of multiple single doses, for example such as a sequence of at least 3 single doses, each single dose consisting of multiple puffs, such as 1, 2, 3 or 4 puffs, preferably 3 or 4 puffs, said sequences being separated from each other by a break period without any inhalation. 
     
     
         25 . The inhaler according to  claim 24  wherein the administration scheme comprises the sequence of csketamine three single doses consisting of 3 or 4 puffs in a period of 30 minutes, single doses being separated by a break periods of 15 minutes, wherein each puff corresponds to esketamine nominal dose of 4 mg in the dry powder composition or formulation. 
     
     
         26 . A method for treatment of depression in a patient in need thereof, the method comprising self-administration of ketamine or its pharmaceutically acceptable salt by said patient by pulmonary route as dry powder inhalable pharmaceutical formulation via an inhaler in a remotely dictated and controlled manner in accordance with the administration scheme prescribed by the attending physician, in the presence of a patient's mobile device with the authorisation token assigned thereto,
 wherein said inhaler is operated in compliance with the administration scheme via a controlled blocking means adopted to allow administration of a pharmaceutical composition only with compliance with the administration scheme and in the presence of a patient's mobile device with the authorisation token assigned thereto.   
     
     
         27 . The method of  claim 26 , wherein said administration scheme is set by the attending physician who generates a control signal comprising said prescribed self-administration scheme and an authorisation token assigned to the subject's mobile device using a control terminal. 
     
     
         28 . The method of  claim 26 , wherein the control signal with the self-administration scheme is received by the inhaler in response to activation and registration of the authorisation token with the inhaler. 
     
     
         29 . The method of  claim 26 , wherein said administration is allowed by the controlled blocking means only with compliance with the administration scheme. 
     
     
         30 . The method of  claim 26  wherein said administration is protected by the remotely controlled blocking means against misuse or abuse by the patient or a third person. 
     
     
         31 . The method according to  claim 26  wherein pharmaceutically acceptable salt is hydrochloride. 
     
     
         32 . The method of  claim 26  wherein ketamine is eskctamine hydrochloride. 
     
     
         33 . The method of  claim 26  wherein the composition comprises from 2 mg to 100 mg of micronized ketamine calculated as a free base per nominal unit dose. 
     
     
         34 . The method according to  claim 33  wherein composition comprises from 2 mg to 40 mg of micronized ketamine calculated as a free base per nominal unit dose. 
     
     
         35 . The method according to  claim 34  wherein the composition comprises 4 mg of micronized esketamine calculated as a free base per nominal unit dose. 
     
     
         36 . The method of  claim 26  wherein composition comprises one or more additives selected from the group consisting of a carbohydrate bulking agent in the amount of 30 to 95% by weight and a stabilizing agent in the amount of 0.2 - 3% by weight, with respect to the total weight of the composition. 
     
     
         37 . The method of  claim 26  wherein composition comprises ketamine having median particle diameter d50 of 1 - 10 μm. d10 of 0.2 - 5 μm and d90 of 3 - 35 μm, as measured by laser diffraction technique. 
     
     
         38 .The method of  claim 34  adopted to provide emitted dose of at least 1.0 mg of ketamine calculated as a free base, corresponding to 1.2 mg of ketamine hydrochloride. 
     
     
         39 . The method according to claim  38  wherein the fraction  5  of the emitted dose delivered to the lungs is at least 40%. 
     
     
         40 . The method of cIaim  26  wherein the composition for administration via pulmonary route is comprised in a blister with plurality of individual nominal unit doses premetered and individually sealed. 
     
     
         41 . The method of  claim 26  wherein the composition for administration via pulmonary route is comprised in a capsule with a single nominal unit dose. 
     
     
         42 . The method of  claim 26  wherein the composition for administration via pulmonary route is comprised in a multi-dose powder reservoir. 
     
     
         43 . The method of  claim 26  wherein the administration scheme provides a self-administration by a patient by inhalation of a dry powder ketamine composition or formulation in a sequence of administrations consisting of multiple single doses, for example such as a sequence of at least 3 single doses, each single dose consisting of multiple puffs, such as 1,2, 3 or 4 puffs, preferably 3 or 4 puffs, said sequences being separated from each other by a break period without any inhalation. 
     
     
         44 . The method according to  claim 43  wherein the administration scheme comprises the sequence of esketamine three single doses consisting of 3 or 4 puffs in a period of 30 minutes, single doses being separated by a break periods of 15 minutes, wherein each puff corresponds to esketamine nominal dose of 4 mg in the dry powder composition or formulation.